DESCRIPTION: The combination of NMR and a separation method provide unmatched structural elucidation capabilities, based primarily on the wealth of chemical information that NMR provides. Unfortunately NMR is an inherently insensitive technique and thus requires large sample masses. The overall goal of this proposal is to improve the mass sensitivity of NMR by two orders of magnitude so that 5-500 nL volumes and picomole masses can be analyzed. The advance that enable such sensitivity improvements is development of miniaturized radiofrequency coils for signal detection in NMR. As the coil diameter is reduced in size it provides much higher signal-to-noise ratios for a given mass of sample. A major portion of this work is the optimization of coil fabrication and design geometry. The nanoliter volume NMR detector cells will be coupled to microseparations. Specifically, optimized flow cells, acquisition parameters, separation modes and preconcentration methods will be developed for capillary electrophoresis and capillary liquid chromatography. In addition to hardware development this proposal seeks to employ to nanoliter NMR method to study the mass limited, but high concentration environment of the interior of a series of peptide containing vesicles from the marine mollusk, Aplysia californica.